Merus N.V. announced that the first patient has been dosed in a Phase 2, open-label, multi-center international clinical trial to evaluate MCLA-128 in two metastatic breast cancer (MBC) populations including HER2-positive MBC patients and hormone receptor positive/HER2-low MBC patients. MCLA-128 is a full-length IgG bispecific antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) targeting HER2 and HER3 receptors. MCLA-128 blocks the HER3 signaling pathway by employing a Dock & Block™ mechanism. MCLA-128 is designed to dock onto a specific region of the HER2 receptor to orientate MCLA-128’s HER3 binding arm to block HER2:HER3 heterodimerization. Oncogenic signaling through the HER3 pathway, even in the presence of high heregulin concentrations, may thus be effectively blocked. The MCLA-128 Phase 2 clinical trial is expected to enroll approximately 120 patients in total across the U.S. and Europe. The first cohort, HER2-positive MBC patients who are progressing on anti-HER2 therapies including TDM-1, will receive MCLA-128 in combination with trastuzumab and chemotherapy. In preclinical studies, synergistic activity of MCLA-128 and trastuzumab has been demonstrated to inhibit heregulin-driven tumor cell growth. The second cohort, MBC patients with confirmed hormone receptor positive status and HER2-low (immuno-histo-chemistry (IHC) HER2 1+ or 2+ and fluorescent in-situ hybridization (FISH) negative for HER2 amplification) who are progressing on hormone therapies and CDK4/6 inhibitors, will receive MCLA-128 in combination with endocrine therapy. In preclinical models, blocking of signaling through the HER3 pathway has been shown to synergize with endocrine therapy. The primary endpoint for both cohorts is the clinical benefit rate at 24 weeks.